The thymus leukemia (TL) antigen is encoded by a mouse Major Histocompatibility Complex (MHC) class I gene that is expressed in the thymus, fetal liver, skin and intestinal epithelium. The function of TL is unknown. We have created several lines of TL (thymus leukemia) antigen transgenic mice that have ectopic expression of TL. All of these transgenic mice show a delay in thymus involution up to the age of at least 11 months, although they are otherwise normal. Cell transfer and organ transplant studies will be carried out to better define the cell type likely to be responsible for the effect of TL on thymus involution. To determine the portion of the TL molecule responsible and gain insight into a possible mechanism of action, gene constructs that encode Ld /TL chimeric class I molecules will be microinjected into mouse eggs to create new lines of transgenic mice. These will be analyzed for thymus size as a function of age. The output of cells from the thymus of older TL transgenic mice will be measured and compared to that in younger mice. Longitudinal studies of serum thymic hormone levels will be performed. The transgenic mice will be evaluated to determine if they exhibit a delay in the senescence of T-cell immune responses that occurs normally in older animals. Reproductive senescence and the lifespan of the transgenic mice will be studied to determine if the delayed involution leads to increased longevity. These TL transgenic mice provide an unparalleled opportunity to study the mechanism of thymus involution, the influence of thymus involution on the senescence of peripheral immune responses, and the relationship between thymus involution and the aging process.